This proposal requests funds for the purchase of a Thermo Scientific LTQ Orbitrap Hybrid FT Mass Spectrometer and Data System. The instrument is linked directly to a Dionex Nano HPLC system affording LC/MS and (MS)n capability and will be located in the Proteomics Center in the Stony Brook School of Medicine. This system will be provide high resolution, accurate mass measurement and electron transfer dissociation, two new mass spectrometer techniques that will significantly promote the research objectives and laboratory productivity of thirteen distinguished scientists from Stony Brook University (SBU) who comprise the major users group. These methods are presently unavailable at SBU and inaccessible or difficult to obtain from other organizations. LC/MS/MS is unsurpassed for the characterization of molecules with a vital biomedical significance, including lipids, biopolymers such as peptides, oligonucleotides, and oligosaccharides and smaller compounds which are non-volatile, labile, or thermally unstable. Techniques for coupling a liquid chromatograph to a mass spectrometer through electrospray or atmospheric pressure chemical ionization sources now permit the routine analysis of these substances with ease and rapidity. Collection of accurate mass data will facilitate protein and small molecule characterization, while the mass analysis of ETD-generated fragment ions will make possible more complete characterization of protein post-translational modifications. New information dependent data acquisition routines permit complete analysis of multiple compounds during a single injection. Quantitative methods employing sensitive LC/MS/MS and iTRAQ techniques are essential for several investigators. The instrument will be operated and maintained by trained personnel at the Proteomics Center, and the Director will schedule daily operation and provide technical expertise for the users. An advisory committee will ensure access to the major users and other PHS-supported investigators and will be responsible for the long term operation of the instrument. PUBLIC HEALTH RELEVANCE Innovative biomedical research requires frequent access to the newest analytical techniques to advance knowledge of human diseases and to provide new treatments for these illnesses. The Thermo Scientific LTQ Orbitrap Hybrid FT Mass Spectrometer and Data System will permit low-level analysis of many biomolecules critical to the research efforts of NIH-supported investigators at Stony Brook. They will use the new, analytical techniques (accurate mass measurement and electron transfer dissociation) offered by this instrument to explore mechanisms leading to diabetes, cancer, and heart disease and help define new biochemical markers and medications for these disease states. [unreadable] [unreadable] [unreadable]